The purpose of this study is to compare a single dose of rifaximin with loperamide to the current standard approach of single dose azithromycin with loperamide for the treatment of acute watery traveler's diarrhea (TD).
The study requires 1) taking a single dose antibiotic plus loperamide to treat TD, 2) providing blood and stool samples at different time points to evaluate infection and immune responses, 3) completing a daily symptom diary following treatment, 4) being seen by the study doctor to monitor illness and recovery, and 5) completing a brief electronic questionnaire at 3 months.
Participants will be randomly assigned to one of the two treatment groups. The two groups are 1) rifaximin 550 mg as a single dose with loperamide 4 mg initially followed by 2 mg after each unformed stool or 2) azithromycin 500 mg as a single dose with loperamide 4 mg initially followed by 2 mg after each unformed stool. Both groups will take the antibiotic dose and 4 mg of loperamide.
Active duty military, 18-60 years old
Presence of acute watery diarrhea (3 or more loose/liquid stools in 24 hours or 2 loose/liquid stools in 24 hours and associated symptoms such as nausea, vomiting, abdominal cramps or tenesmus) lasting <96 hours in duration that impacts function in activities and/or performance of primary duties. Refer to recruitment decision tree below.
Eligible for ambulatory management. (Note: Ambulatory management in this study means that the patient can be treated on an outpatient basis to include up to 23 hours of medical observation and IV therapies.)
Able to comply with follow-up procedures.
Allergy to rifamycins, macrolides, or loperamide (not including mild gastrointestinal upset).
Antibiotic therapy in the 72 hours prior to presentation (excluding malaria prophylaxis with mefloquine, malarone, chloroquine/proguanil, tafenoquine, or doxycycline).
Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, warfarin, chloroquine and hydroxychloroquine).
Current or history of liver disease or other serious health conditions based on review by study physician.
Parallel
Rifaximin 550 MG
DrugRifaximin 550 mg as a single dose administered orally.
Azithromycin 500 MG
DrugAzithromycin 500 mg as a single dose administered orally.
Loperamide
Drug4 mg loperamide administered orally with study antibiotic (rifaximin or azithromycin). Additional loperamide to use as needed, but not to exceed 16 mg/day for 2 days as per licensed use (one 2 mg capsule after each looses stool).
Therapeutic efficacy of single-dose rifaximin (550 mg) with loperamide in treating acute watery diarrhea compared to single-dose azithromycin (500 mg) with loperamide.
Time to last unformed stool (TLUS), in hours, is calculated from the time of antibiotic dose to last unformed (diarrheal) stool (TLUS).
Proportion of participants no longer meeting TD illness criteria at 24 hours
The clinical efficacy cure rate at 24h is the proportion of participants at the 24h follow up after the initial treatment who met the end point of not meeting TD illness.
Proportion of participants no longer meeting TD illness criteria at 72 hours
For the clinical efficacy cure rate at 72h is the proportions of participants who met the end point 1. no report of unformed/diarrheal/loose/liquid stool (LLS) that meet TD illness \>24h after initial treatment and 2. TD-associated symptoms present at 24h were not reported as moderate or greater
Proportion of participants with recurrence of TD illness after previous resolution of TD illness
TD recurrence at 7d follow up if participants meet TD illness and had the previous cure resolution at 24h or 72h
Proportions of serious adverse events (SAE) at 21 days
Proportions of serious adverse events (SAE)
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Henry M. Jackson Foundation for the Advancement of Military Medicine
Lead sponsor
Infectious Diseases Clinical Research Program
Collaborator
Uniformed Services University of the Health Sciences
Collaborator